Huber B, Pette D
Fakultät für Biologie, Universität Konstanz, Germany.
Eur J Biochem. 1996 Mar 15;236(3):814-9. doi: 10.1111/j.1432-1033.1996.t01-2-00814.x.
Similar to previous observations in rabbit muscle, chronic low-frequency stimulation suppressed parvalbumin expression in fast-twitch muscles of the rat. In extensor digitorum longus and tibialis anterior muscles, parvalbumin mRNA levels steeply declined with apparent half-lives of approximately 26 h and 45 h, respectively. Measurements of parvalbumin synthesis indicated that the reduction in mRNA was immediately transmitted to the level of translation. Relative parvalbumin synthesis rates decayed with an apparent half-life of approximately 60 h. Both the decrease in parvalbumin mRNA and synthesis considerably preceded the decay of parvalbumin protein. Although parvalbumin synthesis had approached zero in 14-day-stimulated muscles, parvalbumin content started to decrease only after some delay (28-day-stimulated muscles still contained 40-50% of their normal parvalbumin content). The lag time between fully suppressed synthesis and the onset of parvalbumin decay, as well as the stability of parvalbumin against tryptic cleavage in the presence of Ca2+ and Mg2+, indicated proteolysis as an important post-translational control of parvalbumin levels. The decrease in parvalbumin mRNA followed a similar time course as that of the mRNA specific to the fast myosin heavy chain HCIIb. After complete suppression, parvalbumin mRNA reached control levels 4 days after cessation of stimulation, which demonstrates the complete reversibility of the stimulation-induced parvalbumin suppression. These results show that a slow motoneuron-like impulse pattern rapidly silences the parvalbumin gene, thus overriding fast-fiber-type-specific programs of gene expression. Due to posttranscriptional regulation and the stability of parvalbumin, this high responsiveness of adult skeletal muscle to altered neuromuscular activity is more conspicuous at the mRNA level than at the protein level.
与先前在兔肌肉中的观察结果相似，慢性低频刺激可抑制大鼠快肌中parvalbumin的表达。在趾长伸肌和胫骨前肌中，parvalbumin mRNA水平急剧下降，其表观半衰期分别约为26小时和45小时。parvalbumin合成的测量结果表明，mRNA的减少立即传递到翻译水平。相对parvalbumin合成率以约60小时的表观半衰期衰减。parvalbumin mRNA和合成的减少都明显先于parvalbumin蛋白的降解。尽管在刺激14天的肌肉中parvalbumin合成已接近零，但parvalbumin含量仅在延迟一段时间后才开始下降（刺激28天的肌肉仍含有其正常parvalbumin含量的40 - 50%）。完全抑制合成与parvalbumin降解开始之间的延迟时间，以及parvalbumin在Ca2+和Mg2+存在下对胰蛋白酶切割的稳定性，表明蛋白水解是parvalbumin水平的重要翻译后调控机制。parvalbumin mRNA的减少与快肌球蛋白重链HCIIb特异性mRNA的时间进程相似。完全抑制后，刺激停止4天后parvalbumin mRNA达到对照水平，这证明了刺激诱导的parvalbumin抑制的完全可逆性。这些结果表明，类似慢运动神经元的冲动模式可迅速使parvalbumin基因沉默，从而超越快纤维类型特异性的基因表达程序。由于转录后调控和parvalbumin的稳定性，成年骨骼肌对神经肌肉活动改变的这种高反应性在mRNA水平比在蛋白质水平更为明显。
